Some science behind the scenes

Morphine receptor bindings

Morphine’s opioid binding sites and affinity for those sites is shown below as stated on the IUPHAR database.  As you can see it has a high affinity for the mu receptor with a lesser binding to the delta receptor and moderate binding but only partial at the kappa site.

The kappa binding is interesting, in that it makes the chemical less than ideal in any context, but in most of the papers I studied the majority of the binding that did take place occurred in non-neuronal cells, so its effect on the brain is far less than its effects on the peripheral nervous system.

Receptor

Type

Action

Affinity

μ - mu

Agonist

Full agonist

9.0

κ - kappa

Agonist

Partial agonist

7.3

δ - delta

Agonist

Full agonist

6.9

Mu μ-opioid receptors

We are apparently pre-designed to accept morphine. There is a receptor that only reacts to morphine - the mu3 opiate receptor. Morphine’s main effect is to bind to the ?-opioid receptors.  This is a full agonist action, so all the functions will be active. The binding is strong so the effects will be potent. 

  • Constipation - inhibition of peristaltic action in the intestinal tract. This can cause constipation, a major side effect of μ agonists.
  • Miosis  -  constriction of the pupil of the eyes to less than or equal to two millimeters
  • Hypothermia – suppression of bodily  temperature
  • General pain relief [analgesia] – suppression of pain from wherever it derives
  • Sedation and relaxation - suppression of the need for physical activity
  • Respiratory depression
  • Learning and memory - spatial memory is improved, other types of memory are suppressed 
  • Euphoria and pleasure – via the knock on effects from dopamine release.  “Animal and human studies and clinical experience back up the contention that morphine is one of the most euphoric of drugs”
  • Itching - Histamine release may lead to rash, itching and bronchospasm (in susceptible people).

The Delta receptor

Although morphine is a full agonist [thus it will demonstrate all the functionality of this receptor], its affinity is relatively low, meaning the effects are likely to be less potent than those at the mu receptor.  The main effects here are

  • pain relief - analgesia
  • antidepressant effects –‘ anti-anxiety’
  • Heart arrythmias - Morphine generally has less effect on the cardiovascular system but it may  produce bradycardia and hypotension.

There is also a suggestion that they may have some effect on ‘gastrointestinal motility’. 

The kappa receptor

The kappa binding is interesting, as morphine is not a full agonist, only a partial agonist meaning that some of the functions are missing.  In most of the papers I studied the majority of the binding that did take place occurred in non neuronal cells, so its effect on the brain is far less than its effects on the peripheral nervous system – principally the spinal cord and ‘pain neurons’ in the skin.   The functions are fairly complex, acting both directly and indirectly:

  • Pain relief - Stimulation of relief from abdominal pain and bloating
  • Nausea – and vomiting at higher doses
  • Diuretic - an increase in urine production
  • Cardiovascular – hypertension,  increased cardiac load,  or hypotension, bradycardia, tachycardia
  • Respiratory depression -  at higher doses pulmonary edema occurs when the pressure in blood vessels in the lung is raised because of obstruction to remove blood via the pulmonary veins. Pulmonary edema produces shortness of breath. Pleural effusions may occur when fluid also accumulates in the pleural cavity
  • Visual distortions – possibly caused by the increase [or decrease]  in blood pressure
  • Sexual depressant -  decrease of the normal levels of sex hormones ; orgasm might be difficult - at high levels it can lead to impotence.  But It may be worth noting that, Li Shizhen in his Compendium of Materia Medica (1578), wrote that "lay people use it for the art of sex," in particular the ability to "arrest seminal emission." .  So on the positive side it helps with premature ejaculation. 
  • Hair thinning - delay of hair regrowth leading to balding
  • Brain neuron increase -  the populating of the growing brain with neurons

The 5-HT3 receptor

Fairly recent research has indicated that there may be a specific interaction with 5-HT(3A) receptors.  The 5-HT3 receptor differs markedly in structure and mechanism from the other 5-HT receptor subtypes.   When the receptor is affected by agonists  it causes:

  • nausea and vomiting
  • a propensity for seizures

The sigma receptor

It has been shown that sigma σ-agonists, such as (+)-pentazocine, antagonize morphine analgesia, and sigma σ-antagonists enhance morphine analgesia, suggesting some interaction between morphine and the σ-opioid receptor.  At present it is not known what the effects are.

A Summary of effects from morphine

Positive

  • General pain relief [analgesia]
  • Sedation and relaxation
  • Empathy, loving feelings, sociability
  • Spatial memory and learning ability, neuron increase
  • Euphoria and pleasure

Negative

  • Constipation
  • Miosis and Visual distortions
  • Hypothermia
  • Respiratory depression -   pulmonary edema, shortness of breath, pleural effusions
  • Itching
  • Heart problems - hypertension or hypotension, bradycardia, tachycardia
  • Nausea and Vomiting
  • Increase in urine production
  • Sexual depression
  • Hair thinning